BPTF

Summary

BPTF (bromodomain PHD finger transcription factor, HGNC:3581) is a protein-coding gene on chromosome 17q24.2, encoding Nucleosome-remodeling factor subunit BPTF (Q12830). Regulatory subunit of the ATP-dependent NURF-1 and NURF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair. It is a selective cancer dependency (DepMap: 68.0% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene was identified by the reactivity of its encoded protein to a monoclonal antibody prepared against brain homogenates from patients with Alzheimer’s disease. Analysis of the original protein (fetal Alz-50 reactive clone 1, or FAC1), identified as an 810 aa protein containing a DNA-binding domain and a zinc finger motif, suggested it might play a role in the regulation of transcription. High levels of FAC1 were detected in fetal brain and in patients with neurodegenerative diseases. The protein encoded by this gene is actually much larger than originally thought, and it also contains a C-terminal bromodomain characteristic of proteins that regulate transcription during proliferation. The encoded protein is highly similar to the largest subunit of the Drosophila NURF (nucleosome remodeling factor) complex. In Drosophila, the NURF complex, which catalyzes nucleosome sliding on DNA and interacts with sequence-specific transcription factors, is necessary for the chromatin remodeling required for transcription. Two alternative transcripts encoding different isoforms have been described completely.

Source: NCBI Gene 2186 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic intellectual disability (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 41
• Clinical variants (ClinVar): 1,200 total — 44 pathogenic, 31 likely-pathogenic
• Phenotypes (HPO): 75
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 68.0% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_182641

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3581
Approved symbol	BPTF
Name	bromodomain PHD finger transcription factor
Location	17q24.2
Locus type	gene with protein product
Status	Approved
Aliases	FAC1, NURF301
Ensembl gene	ENSG00000171634
Ensembl biotype	protein_coding
OMIM	601819
Entrez	2186

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 12 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000306378, ENST00000321892, ENST00000342579, ENST00000424123, ENST00000467104, ENST00000544491, ENST00000544778, ENST00000577770, ENST00000577837, ENST00000578307, ENST00000579173, ENST00000580465, ENST00000581258, ENST00000582406, ENST00000582467, ENST00000583990, ENST00000584931, ENST00000644067

RefSeq mRNA: 2 — MANE Select: NM_182641 NM_004459, NM_182641

CCDS: CCDS11673

Canonical transcript exons

ENST00000306378 — 28 exons

Exon	Start	End
ENSE00001223457	67945409	67946325
ENSE00002431219	67918714	67918838
ENSE00002450094	67929336	67929487
ENSE00002458783	67947726	67947808
ENSE00002460084	67853940	67854762
ENSE00002461925	67893370	67893725
ENSE00002463926	67966572	67966656
ENSE00002465965	67866464	67866687
ENSE00002469197	67944150	67944372
ENSE00002470855	67920015	67920143
ENSE00002474914	67928355	67928601
ENSE00002475711	67891844	67892034
ENSE00002478848	67909582	67909761
ENSE00002481885	67910877	67913187
ENSE00002484050	67931911	67932019
ENSE00002488255	67964212	67964404
ENSE00002491113	67982252	67984378
ENSE00002492370	67903789	67903918
ENSE00002499983	67904702	67904840
ENSE00002506993	67874817	67875020
ENSE00002511387	67922840	67922990
ENSE00002511628	67948081	67948306
ENSE00002534782	67924547	67924589
ENSE00002689718	67825503	67826337
ENSE00002719721	67959541	67959875
ENSE00003489588	67940439	67940656
ENSE00003518015	67975772	67975958
ENSE00003753047	67894034	67894165

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 97.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.6030 / max 293.3452, expressed in 1812 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162351	24.5050	1804
162352	1.6381	964
162353	0.7017	408
162357	0.6829	359
208357	0.0753	27

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	97.66	gold quality
ventricular zone	UBERON:0003053	97.54	gold quality
cortical plate	UBERON:0005343	96.95	gold quality
ganglionic eminence	UBERON:0004023	96.32	gold quality
corpus callosum	UBERON:0002336	96.29	gold quality
cerebellar hemisphere	UBERON:0002245	96.08	gold quality
cerebellar cortex	UBERON:0002129	96.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.98	gold quality
colonic epithelium	UBERON:0000397	95.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.70	gold quality
cerebellum	UBERON:0002037	95.56	gold quality
tonsil	UBERON:0002372	95.14	gold quality
left ovary	UBERON:0002119	94.82	gold quality
trabecular bone tissue	UBERON:0002483	94.72	gold quality
calcaneal tendon	UBERON:0003701	94.71	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.59	gold quality
adrenal tissue	UBERON:0018303	94.56	gold quality
renal medulla	UBERON:0000362	94.55	gold quality
tibial nerve	UBERON:0001323	94.30	gold quality
pituitary gland	UBERON:0000007	94.20	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.18	gold quality
lower lobe of lung	UBERON:0008949	94.11	gold quality
right ovary	UBERON:0002118	94.06	gold quality
pylorus	UBERON:0001166	94.05	gold quality
skin of abdomen	UBERON:0001416	93.97	gold quality
body of uterus	UBERON:0009853	93.93	gold quality
skin of leg	UBERON:0001511	93.85	gold quality
endocervix	UBERON:0000458	93.73	gold quality
cardia of stomach	UBERON:0001162	93.71	gold quality
right testis	UBERON:0004534	93.70	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	440.12
E-MTAB-6524	no	250.27
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
EN1
EN2
HOXC8	Unknown
MAZ

miRNA regulators (miRDB)

257 targeting BPTF, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-607	99.97	73.62	5593

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 68.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 25)

• hkelch-like ECH-associated protein 1 regulates FAC1 in addition to its known role in control of Nrf2 (PMID:15379550)
• These findings suggest a role for FAC1 in apoptosis following release of Nrf2 from Keap1 in response to oxidative stress. (PMID:16137655)
• crystallographic and NMR structures of the bromodomain-proximal PHD finger of BPTF in free and H3(1-15)K4me3-bound states (PMID:16728978)
• High FALZ expression is associated with metastatic spread to the brain in primary non-small cell lung cancer. (PMID:19190132)
• the novel translocation breakpoint within the BPTF gene is associated with a pre-malignant phenotype (PMID:20300178)
• The PHD-adjacent bromodomain in BPTF binds with marked selectivity H4K16ac, in combination with H3K4me3 at the mononucleosome level. (PMID:21596426)
• expression may be marker for survival prediction in hepatocellular carcinoma (PMID:25362514)
• High BPTF expression was significantly correlated with tumor progression and may be a potent prognostic marker of colorectal cancer. (PMID:25716692)
• BPTF plays an essential role in cell growth and survival by targeting multiply signaling pathways in human lung cancers (PMID:26418899)
• somatic frameshift mutations of BPTF were present in gastric cancer and colorectal cancers (PMID:26899553)
• NRP2 inhibits WDFY1 transcription by preventing the nuclear localization of a transcription factor, Fetal ALZ50-reactive clone 1 (FAC1). (PMID:27026195)
• Overexpression of BPTF is associated with melanoma cell survival and progression. (PMID:27185926)
• Two new signals were observed at genome-wide significance (P < 5 x 10-8), namely, rs7216064 (17q24.3, BPTF), for overall lung adenocarcinoma risk, and rs3817963 (6p21.3, BTNL2) which is specific to cases with EGFR mutations. In further sub-analyses by EGFR status, rs9387478 (ROS1/DCBLD1) and rs2179920 (HLA-DPB1) showed stronger estimated associations in EGFR-positive compared to EGFR-negative cases (PMID:28025329)
• Haploinsufficiency of BPTF gene is associated with Syndromic Developmental and Speech Delay, Postnatal Microcephaly, and Dysmorphic Features. (PMID:28942966)
• Study identified a novel NSUN2 methylated lncRNA (NMR), which was significantly upregulated in esophageal squamous cell carcinoma (ESCC), functioned as a key regulator of ESCC tumor metastasis and drug resistance. NMR could directly bind to chromatin regulator BPTF, and potentially promote MMP3 and MMP10 expression by ERK1/2 pathway through recruiting BPTF to chromatin. (PMID:29763634)
• data indicate that miR-3666 could play an essential role in cell proliferation, migration, and invasiveness by targeting BPTF and partly inhibiting the PI3K-AKT and EMT signaling pathways in human lung cancers (PMID:30481052)
• High BPTF expression in glioma tissue specimens was significantly associated with WHO grade and tumor size. Survival analysis revealed that the BPTF highexpression group had poorer overall and progressionfree survival compared with the lowexpression group. (PMID:30542695)
• High BPTF expression is associated with gastric cancer growth and invasion. (PMID:30922402)
• Upregulation of bromodomain PHD finger transcription factor in ovarian cancer and its critical role for cancer cell proliferation and survival. (PMID:32985220)
• Downregulated METTL14 accumulates BPTF that reinforces super-enhancers and distal lung metastasis via glycolytic reprogramming in renal cell carcinoma. (PMID:33664855)
• The effect of growth hormone treatment in children with novel BPTF gene variants: A report of two cases and literature review. (PMID:36153657)
• Targeting regulation of VEGF by BPTF in non-small cell lung cancer and its potential clinical significance. (PMID:36529788)
• PHF6 recruits BPTF to promote HIF-dependent pathway and progression in YAP-high breast cancer. (PMID:36967443)
• A role of BPTF in viral oncogenicity delineated through studies of heritable Kaposi sarcoma. (PMID:38380509)
• NUP98-BPTF promotes oncogenic transformation through PIM1 upregulation. (PMID:38940430)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bptf	ENSDARG00000077361
mus_musculus	Bptf	ENSMUSG00000040481
rattus_norvegicus	Bptf	ENSRNOG00000047296
drosophila_melanogaster	E(bx)	FBGN0000541

Paralogs (11): BAZ1B (ENSG00000009954), BAZ2A (ENSG00000076108), CECR2 (ENSG00000099954), KAT2A (ENSG00000108773), KAT2B (ENSG00000114166), BAZ2B (ENSG00000123636), BRDT (ENSG00000137948), BRD4 (ENSG00000141867), BRD3 (ENSG00000169925), BAZ1A (ENSG00000198604), BRD2 (ENSG00000204256)

Protein

Protein identifiers

Nucleosome-remodeling factor subunit BPTF — Q12830 (reviewed: Q12830)

Alternative names: Bromodomain and PHD finger-containing transcription factor, Fetal Alz-50 clone 1 protein, Fetal Alzheimer antigen

All UniProt accessions (11): A0A2R8Y7Q1, E7ETD6, E9PE19, Q12830, F5GXF5, F5H176, J3KSK9, J3KSY0, J3QLW4, J3QQK4, J3QQQ8

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the ATP-dependent NURF-1 and NURF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair. The NURF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the NURF-5 ISWI chromatin remodeling complex. Within the NURF-1 ISWI chromatin-remodeling complex, binds to the promoters of En1 and En2 to positively regulate their expression and promote brain development. Histone-binding protein which binds to H3 tails trimethylated on ‘Lys-4’ (H3K4me3), which mark transcription start sites of active genes. Binds to histone H3 tails dimethylated on ‘Lys-4’ (H3K4Me2) to a lesser extent. May also regulate transcription through direct binding to DNA or transcription factors.

Subunit / interactions. Interacts with MAZ. Interacts with KEAP1. Component of the NURF-1 ISWI chromatin remodeling complex (also called the nucleosome-remodeling factor (NURF) complex) at least composed of SMARCA1 (isoform 2), BPTF, RBBP4 and RBBP7. Within the complex interacts with isoform 2 of SMARCA1. Component of the BPFT-SMARCA1 complex at least composed of SMARCA1 (isoform 1), BPFT, RBBP4 and RBBP7; the complex is catalytically inactive and does not remodel chromatin. Within the complex interacts with isoform 1 of SMARCA1. Component of the NURF-5 ISWI chromatin remodeling complex at least composed of SMARCA5/SNF2H and BPTF. Within NURF-5 ISWI chromatin remodeling complex interacts with SMARCA5/SNF2H.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitously expressed, with highest levels in testis. Present in kidney, liver and brain. In the brain, highest levels are found in motor cortex (at protein level).

Post-translational modifications. Phosphorylation enhances DNA-binding. Highly susceptible to proteolysis.

Disease relevance. Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL) [MIM:617755] An autosomal dominant neurodevelopmental disorder characterized by variable degrees of developmental delay, intellectual disability, speech delay, postnatal microcephaly, dysmorphic features, and mild abnormalities of the hands and feet. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The second PHD-type zinc finger mediates binding to histone H3K4Me3. Has specificity for trimethyllysine; introducing a mutation in the Tyr-2876 residue can induce binding to dimethyllysine.

Similarity. Belongs to the PBTF family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q12830-1	1	yes
Q12830-2	2
Q12830-4	4

RefSeq proteins (2): NP_004450, NP_872579* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001487	Bromodomain	Domain
IPR001965	Znf_PHD	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR018359	Bromodomain_CS	Conserved_site
IPR018501	DDT_dom	Domain
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR019787	Znf_PHD-finger	Domain
IPR028941	WHIM2_dom	Domain
IPR036427	Bromodomain-like_sf	Homologous_superfamily
IPR038028	BPTF	Family

Pfam: PF00439, PF00628, PF02791, PF15613

UniProt features (129 total): compositionally biased region 35, sequence conflict 17, region of interest 16, modified residue 16, helix 11, mutagenesis site 8, coiled-coil region 4, site 4, cross-link 4, sequence variant 3, domain 2, turn 2, strand 2, zinc finger region 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

45 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8AG2	X-RAY DIFFRACTION	1.02
5R4O	X-RAY DIFFRACTION	1.05
5R4M	X-RAY DIFFRACTION	1.11
5R4L	X-RAY DIFFRACTION	1.13
5R4K	X-RAY DIFFRACTION	1.17
5R4H	X-RAY DIFFRACTION	1.18
7K6S	X-RAY DIFFRACTION	1.23
5R4G	X-RAY DIFFRACTION	1.25
5R4I	X-RAY DIFFRACTION	1.28
5R4N	X-RAY DIFFRACTION	1.28
5R4J	X-RAY DIFFRACTION	1.39
7LPK	X-RAY DIFFRACTION	1.39
7RWN	X-RAY DIFFRACTION	1.39
7LRK	X-RAY DIFFRACTION	1.44
2RI7	X-RAY DIFFRACTION	1.45
7LRO	X-RAY DIFFRACTION	1.45
3QZT	X-RAY DIFFRACTION	1.5
7KDZ	X-RAY DIFFRACTION	1.54
7F5D	X-RAY DIFFRACTION	1.57
3UV2	X-RAY DIFFRACTION	1.58
7RWO	X-RAY DIFFRACTION	1.58
7K6R	X-RAY DIFFRACTION	1.6
8OU2	X-RAY DIFFRACTION	1.6
7LP0	X-RAY DIFFRACTION	1.66
7KDW	X-RAY DIFFRACTION	1.71
7RWP	X-RAY DIFFRACTION	1.73
7M2E	X-RAY DIFFRACTION	1.75
3QZS	X-RAY DIFFRACTION	1.8
7VD4	X-RAY DIFFRACTION	1.86
6LU5	X-RAY DIFFRACTION	1.87

Predicted structure (AlphaFold)

No AlphaFold model available for Q12830 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (4): 2869 (histone h3k4me3 binding); 2876 (histone h3k4me3 binding); 2882 (histone h3k4me3 binding); 2891 (histone h3k4me3 binding)

Post-translational modifications (20): 216, 572, 763, 817, 880, 1064, 1231, 1300, 1303, 1310, 2098, 2155, 2162, 2184, 2191, 2465, 1088, 1138, 1209, 1730

Mutagenesis-validated functional residues (8):

Position	Phenotype
2869	abolishes binding to histone h3k4me3.
2876	induces binding to histone h3k4me2.
2876	strongly reduces binding to histone h3k4me3.
2882	abolishes binding to histone h3k4me3.
2884	strongly reduces binding to histone h3k4me3.
2886	abolishes binding to histone h3k4me3.
2889	strongly reduces binding to histone h3k4me3.
2891	abolishes binding to histone h3k4me3.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 432 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GCANCTGNY_MYOD_Q6, CTATGCA_MIR153, AATGGAG_MIR136, BONCI_TARGETS_OF_MIR15A_AND_MIR16_1, PATIL_LIVER_CANCER, GOBP_RESPONSE_TO_NERVE_GROWTH_FACTOR, GOBP_EMBRYONIC_PLACENTA_DEVELOPMENT, CATTTCA_MIR203, SOX9_B1, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_ANTERIOR_POSTERIOR_PATTERN_SPECIFICATION, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, GOBP_ENDODERM_DEVELOPMENT, GOBP_HEAD_DEVELOPMENT

GO Biological Process (12): negative regulation of transcription by RNA polymerase II (GO:0000122), embryonic placenta development (GO:0001892), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), brain development (GO:0007420), endoderm development (GO:0007492), anterior/posterior pattern specification (GO:0009952), positive regulation of transcription by RNA polymerase II (GO:0045944), cellular response to nerve growth factor stimulus (GO:1990090), chromatin organization (GO:0006325), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (6): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), protein binding (GO:0005515), ATP-dependent activity, acting on DNA (GO:0008094), metal ion binding (GO:0046872)

GO Cellular Component (10): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), NURF complex (GO:0016589), dendrite (GO:0030425), cell body (GO:0044297), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), ATPase complex (GO:1904949)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
transcription by RNA polymerase II	3
regulation of transcription by RNA polymerase II	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
negative regulation of DNA-templated transcription	1
in utero embryonic development	1
placenta development	1
embryonic organ development	1
chromatin organization	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
central nervous system development	1
animal organ development	1
head development	1
tissue development	1
regionalization	1
positive regulation of DNA-templated transcription	1
cellular response to growth factor stimulus	1
response to nerve growth factor	1
cellular component organization	1
negative regulation of RNA biosynthetic process	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
transition metal ion binding	1
DNA binding	1
binding	1
ATP hydrolysis activity	1
catalytic activity, acting on DNA	1
ATP-dependent activity	1
cation binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
ISWI-type complex	1
neuron projection	1
dendritic tree	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

2320 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BPTF	SMARCA1	P28370	996
BPTF	H3-3A	P06351	959
BPTF	H3C1	P02295	959
BPTF	H3-4	Q16695	959
BPTF	H3-7	Q5TEC6	959
BPTF	H3-5	Q6NXT2	959
BPTF	H3C14	Q71DI3	959
BPTF	SMARCA5	O60264	955
BPTF	RBBP4	P31149	847
BPTF	ING2	Q9H160	774
BPTF	H4C7	Q99525	749
BPTF	H4C16	P02304	748
BPTF	WDR5	P61964	744
BPTF	ING3	Q9NXR8	742
BPTF	H2AZ1	P0C0S5	739

IntAct

98 interactions, top by confidence:

A	B	Type	Score
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
SMARCA1	RBBP4	psi-mi:“MI:0914”(association)	0.770
SMARCA1	RBBP4	psi-mi:“MI:0915”(physical association)	0.770
SMARCA1	BPTF	psi-mi:“MI:0915”(physical association)	0.750
BPTF	SMARCA1	psi-mi:“MI:0914”(association)	0.750
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
DPY30	AKAP8	psi-mi:“MI:0914”(association)	0.610
BPTF	SMARCA5	psi-mi:“MI:0915”(physical association)	0.560
DPY30	BPTF	psi-mi:“MI:0914”(association)	0.530
CBX6	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
SMARCA5	RBBP4	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530
RBBP7	SMARCA5	psi-mi:“MI:0914”(association)	0.530
BACC1	SMARCA1	psi-mi:“MI:0914”(association)	0.530
RBBP7	EPOP	psi-mi:“MI:0914”(association)	0.530
BACC1	SMARCA5	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
	BPTF	psi-mi:“MI:0407”(direct interaction)	0.440
BPTF	H4C16	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (264): BPTF (Protein-peptide), BPTF (Affinity Capture-MS), BPTF (Affinity Capture-MS), BPTF (Affinity Capture-MS), H3.1 (Reconstituted Complex), BPTF (Affinity Capture-MS), BPTF (Affinity Capture-MS), BPTF (Co-fractionation), BPTF (Co-fractionation), BPTF (Co-fractionation), TFAP4 (Co-fractionation), BPTF (Affinity Capture-MS), BPTF (Affinity Capture-MS), BPTF (Affinity Capture-MS), BPTF (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IZ84, A0A1L8H8C0, A0A1L8HFX9, A2RUV4, F1LP90, F5HSE3, O43310, O60237, O75167, O88453, P41110, P61406, Q12830, Q1LVF3, Q2HJG4, Q2PFD7, Q3TLH4, Q5RAK6, Q5ZMS6, Q66HC1, Q6A0A2, Q6NRP6, Q6NZL0, Q6P1U3, Q6PKG0, Q75N33, Q7TN02, Q7TPM1, Q7YZA2, Q7Z6E9, Q80TN7, Q80XI3, Q86UR5, Q86US8, Q8IVL0, Q8IVL1, Q8K0V4, Q8N4C8, Q90YL3, Q90YY5

Diamond homologs: A0A0R4IXF6, A0A7U2QYM2, A2AHJ4, A2AUY4, A2BIL7, B2RRD7, B7ZS37, D4A7T3, E9Q2Z1, F1QW93, F1R5H6, F7DRV9, G5E8P1, O15164, O60885, O74350, O88379, O88665, O95696, P13709, P21675, P25440, P35817, P51123, P53236, P54816, P55201, P87152, Q02206, Q03330, Q07442, Q08D75, Q09948, Q12830, Q15059, Q1LUC3, Q23590, Q32S26, Q338B9, Q4R8Y1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
BPTF	“form complex”	HNuRF	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 108 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
PRC2 methylates histones and DNA	8	16.7×	3e-06
NuRD complex assembly	8	15.4×	4e-06
Deposition of new CENPA-containing nucleosomes at the centromere	7	15.2×	2e-05
Defective pyroptosis	7	15.0×	2e-05
Regulation of PD-L1(CD274) transcription	10	14.9×	4e-07
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	7	14.6×	2e-05
FXIIa activates plasma kallikrein-kinin system	6	14.2×	1e-04
Interaction of NuRD complexes with transcription factors	8	13.9×	8e-06

GO biological processes:

GO term	Partners	Fold	FDR
nucleosome assembly	9	12.5×	1e-05
chromatin remodeling	11	8.0×	2e-05
transcription by RNA polymerase II	11	7.7×	3e-05
chromatin organization	7	6.9×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1200 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	44
Likely pathogenic	31
Uncertain significance	696
Likely benign	266
Benign	52

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071837	NM_182641.4(BPTF):c.4469del (p.Ser1490fs)	Pathogenic
1174080	NM_182641.4(BPTF):c.5575_5576del (p.Arg1859fs)	Pathogenic
1319921	NM_182641.4(BPTF):c.1999C>T (p.Gln667Ter)	Pathogenic
1319947	NM_182641.4(BPTF):c.7960_7961del (p.Glu2654fs)	Pathogenic
1330710	NM_182641.4(BPTF):c.6562_6563del (p.Val2188fs)	Pathogenic
1335295	NM_182641.4(BPTF):c.5301del (p.Thr1766_Trp1767insTer)	Pathogenic
1693351	NM_182641.4(BPTF):c.5212C>T (p.Arg1738Ter)	Pathogenic
1693493	NM_182641.4(BPTF):c.209dup (p.Ser71fs)	Pathogenic
1694861	NM_182641.4(BPTF):c.4035_4036del (p.Cys1345_Glu1346delinsTer)	Pathogenic
1802122	NM_182641.4(BPTF):c.7162C>T (p.Gln2388Ter)	Pathogenic
2536022	NM_182641.4(BPTF):c.7037_7040dup (p.Gln2348fs)	Pathogenic
3062168	NM_182641.4(BPTF):c.8649del (p.Ser2883fs)	Pathogenic
3068507	NM_182641.4(BPTF):c.7776dup (p.Arg2593fs)	Pathogenic
3254960	NM_182641.4(BPTF):c.3157_3158del (p.Lys1053fs)	Pathogenic
3342506	NM_182641.4(BPTF):c.3074_3075del (p.Glu1025fs)	Pathogenic
3377266	NM_182641.4(BPTF):c.5854dup (p.Ala1952fs)	Pathogenic
3381404	NM_182641.4(BPTF):c.2521C>T (p.Arg841Ter)	Pathogenic
3481708	NM_182641.4(BPTF):c.2060_2061delinsACCA (p.Leu687fs)	Pathogenic
3677167	NM_182641.4(BPTF):c.4177C>T (p.Arg1393Ter)	Pathogenic
3679943	NM_182641.4(BPTF):c.8572C>T (p.Arg2858Ter)	Pathogenic
3906923	GRCh37/hg19 17q24.2(chr17:65870603-65971611)x1	Pathogenic
3992532	NM_182641.4(BPTF):c.3970C>T (p.Gln1324Ter)	Pathogenic
4214990	NM_182641.4(BPTF):c.202del (p.Arg68fs)	Pathogenic
431064	NM_182641.4(BPTF):c.2482dup (p.Glu828fs)	Pathogenic
431065	NM_182641.4(BPTF):c.4838_4839del (p.Val1613fs)	Pathogenic
431066	NM_182641.4(BPTF):c.8701A>T (p.Lys2901Ter)	Pathogenic
431067	Single allele	Pathogenic
431068	Single allele	Pathogenic
431069	NM_182641.4(BPTF):c.2982_2992+1del	Pathogenic
431072	NM_182641.4(BPTF):c.989del (p.Leu330fs)	Pathogenic

SpliceAI

5223 predictions. Top by Δscore:

Variant	Effect	Δscore
17:67853938:A:AG	acceptor_gain	1.0000
17:67853938:AG:A	acceptor_gain	1.0000
17:67853939:G:GA	acceptor_loss	1.0000
17:67853939:G:GG	acceptor_gain	1.0000
17:67853939:GG:G	acceptor_gain	1.0000
17:67853939:GGT:G	acceptor_gain	1.0000
17:67853939:GGTA:G	acceptor_gain	1.0000
17:67854758:ATAAT:A	donor_gain	1.0000
17:67854759:TAAT:T	donor_gain	1.0000
17:67854760:AAT:A	donor_gain	1.0000
17:67854760:AATG:A	donor_loss	1.0000
17:67854761:AT:A	donor_gain	1.0000
17:67854761:ATGTA:A	donor_loss	1.0000
17:67854762:TG:T	donor_loss	1.0000
17:67854763:G:GG	donor_gain	1.0000
17:67854767:G:GG	donor_gain	1.0000
17:67866458:A:AG	acceptor_gain	1.0000
17:67866462:A:AG	acceptor_gain	1.0000
17:67866463:G:GG	acceptor_gain	1.0000
17:67866463:GA:G	acceptor_gain	1.0000
17:67866683:TAATG:T	donor_loss	1.0000
17:67866684:AATG:A	donor_loss	1.0000
17:67866685:ATGGT:A	donor_loss	1.0000
17:67866689:T:A	donor_loss	1.0000
17:67874806:A:AG	acceptor_gain	1.0000
17:67874807:C:G	acceptor_gain	1.0000
17:67874808:A:AG	acceptor_gain	1.0000
17:67874809:C:G	acceptor_gain	1.0000
17:67874810:A:AG	acceptor_gain	1.0000
17:67874811:T:G	acceptor_gain	1.0000

AlphaMissense

19204 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:67825729:G:T	R2M	1.000
17:67826283:A:C	S187R	1.000
17:67826285:T:A	S187R	1.000
17:67826285:T:G	S187R	1.000
17:67826298:A:C	S192R	1.000
17:67826300:C:A	S192R	1.000
17:67826300:C:G	S192R	1.000
17:67826301:A:C	S193R	1.000
17:67826303:C:A	S193R	1.000
17:67826303:C:G	S193R	1.000
17:67854239:T:C	F305L	1.000
17:67854241:T:A	F305L	1.000
17:67854241:T:G	F305L	1.000
17:67854242:G:A	G306R	1.000
17:67854242:G:C	G306R	1.000
17:67854243:G:A	G306E	1.000
17:67854260:G:C	D312H	1.000
17:67854263:A:C	S313R	1.000
17:67854265:C:A	S313R	1.000
17:67854265:C:G	S313R	1.000
17:67854302:T:A	W326R	1.000
17:67854302:T:C	W326R	1.000
17:67854318:G:C	R331P	1.000
17:67854332:A:C	S336R	1.000
17:67854334:T:A	S336R	1.000
17:67854334:T:G	S336R	1.000
17:67854441:T:C	L372P	1.000
17:67854456:C:A	A377D	1.000
17:67854459:G:C	R378P	1.000
17:67854494:G:C	D390H	1.000

dbSNP variants (sampled 300 via entrez): RS1000006840 (17:67879125 G>C,T), RS1000010057 (17:67968140 T>G), RS1000064370 (17:67899752 G>A), RS1000114490 (17:67907991 T>C), RS1000133307 (17:67936566 C>G), RS1000171354 (17:67865730 C>A), RS1000208385 (17:67873919 G>A), RS1000247379 (17:67862689 A>G), RS1000348180 (17:67908569 T>A,C), RS1000397516 (17:67907707 C>T), RS1000404996 (17:67863083 G>C), RS1000414471 (17:67915740 A>G), RS1000414595 (17:67828546 GAGA>G), RS1000466910 (17:67916096 C>A,G,T), RS1000505636 (17:67936799 G>A)

Disease associations

OMIM: gene MIM:601819 | disease phenotypes: MIM:617755, MIM:148000

GenCC curated gene-disease

Disease	Classification	Inheritance
syndromic intellectual disability	Strong	Autosomal dominant
neurodevelopmental disorder with dysmorphic facies and distal limb anomalies	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
syndromic intellectual disability	Definitive	AD

Mondo (8): neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (MONDO:0060596), neurodevelopmental disorder (MONDO:0700092), intellectual disability (MONDO:0001071), Kaposi’s sarcoma (MONDO:0005055), Kaposi sarcoma, susceptibility to (MONDO:0007845), syndromic intellectual disability (MONDO:0000508), vascular disorder (MONDO:0005385), microcephaly (MONDO:0001149)

Orphanet (4): BPTF-related intellectual disability-facial dysmorphism-skeletal anomalies syndrome (Orphanet:686482), Kaposi sarcoma (Orphanet:33276), Rare genetic syndromic intellectual disability (Orphanet:183763), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

75 total (30 of 75 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000076	Vesicoureteral reflux
HP:0000160	Narrow mouth
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000347	Micrognathia
HP:0000362	Otosclerosis
HP:0000403	Recurrent otitis media
HP:0000431	Wide nasal bridge
HP:0000448	Prominent nose
HP:0000455	Broad nasal tip
HP:0000470	Short neck
HP:0000475	Broad neck
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000545	Myopia
HP:0000574	Thick eyebrow
HP:0000582	Upslanted palpebral fissure
HP:0000664	Synophrys
HP:0000692	Tooth malposition
HP:0000708	Atypical behavior
HP:0000712	Emotional lability
HP:0000718	Aggressive behavior
HP:0000738	Hallucinations
HP:0000739	Anxiety

GWAS associations

41 associations (top):

Study	Trait	p-value
GCST001609_3	Lung adenocarcinoma	7.000000e-11
GCST001740_3	Lung cancer	7.000000e-06
GCST003538_6	Alcohol dependence symptom count	5.000000e-07
GCST003605_5	EGFR mutation-positive lung adenocarcinoma	2.000000e-12
GCST004600_147	Eosinophil percentage of white cells	9.000000e-18
GCST004606_27	Eosinophil count	6.000000e-19
GCST004617_126	Eosinophil percentage of granulocytes	4.000000e-17
GCST004623_87	Neutrophil percentage of granulocytes	8.000000e-15
GCST004624_9	Sum eosinophil basophil counts	2.000000e-17
GCST004904_192	Body mass index	6.000000e-12
GCST004904_217	Body mass index	5.000000e-10
GCST005829_17	Hand grip strength	5.000000e-12
GCST005830_13	Hand grip strength	1.000000e-16
GCST006464_26	Endometrial cancer	4.000000e-07
GCST006465_4	Endometrial cancer (endometrioid histology)	4.000000e-06
GCST006611_61	HDL cholesterol	3.000000e-11
GCST006922_1	Regular attendance at a religious group	2.000000e-06
GCST006923_7	Loneliness	6.000000e-09
GCST006924_5	Loneliness (MTAG)	1.000000e-09
GCST006976_111	Macular thickness	7.000000e-12
GCST007323_19	Risk-taking tendency (4-domain principal component model)	1.000000e-08
GCST008479_30	Psoriasis	2.000000e-08
GCST008834_21	Non-small cell lung cancer	2.000000e-09
GCST008839_282	Height	7.000000e-11
GCST009379_213	Type 2 diabetes	6.000000e-08
GCST009379_214	Type 2 diabetes	7.000000e-06
GCST009379_215	Type 2 diabetes	3.000000e-11
GCST009463_10	Loneliness	7.000000e-09
GCST009463_11	Loneliness	5.000000e-08
GCST009602_72	Metabolic syndrome	8.000000e-09

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0007835	alcohol dependence measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0004340	body mass index
EFO:0006941	grip strength measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009592	social interaction measurement
EFO:0007865	loneliness measurement
EFO:0008579	risk-taking behaviour
EFO:0000195	metabolic syndrome
EFO:0004530	triglyceride measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004346	neuroimaging measurement
EFO:0009749	age at first sexual intercourse measurement
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D012514	Sarcoma, Kaposi	C01.925.256.466.860; C04.557.450.795.850; C04.557.645.750
D014652	Vascular Diseases	C14.907

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3085621 (SINGLE PROTEIN), CHEMBL6195548 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,716 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL130880	IPIDACRINE	2	821
CHEMBL513909	BI-2536	2	895

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Non-enzymatic BRD containing proteins

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
MS363	Inhibition	5.79	pKi

ChEMBL bioactivities

79 potent at pChembl≥5 of 110 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.20	Kd	6.3	nM	CHEMBL4872300
8.03	Kd	9.3	nM	CHEMBL4861491
7.80	IC50	16	nM	CHEMBL4873093
7.80	IC50	16	nM	CHEMBL4860578
7.80	IC50	16	nM	CHEMBL4780673
7.57	IC50	26.9	nM	CHEMBL4873042
7.54	IC50	28.8	nM	CHEMBL4870170
7.52	IC50	30	nM	CHEMBL4873093
7.52	IC50	30	nM	CHEMBL4780673
7.49	IC50	32.7	nM	CHEMBL4867072
7.44	IC50	36	nM	CHEMBL4861491
7.43	IC50	36.9	nM	CHEMBL4868713
7.41	IC50	39	nM	CHEMBL6189123
7.25	IC50	56	nM	CHEMBL4848701
7.23	IC50	59.3	nM	CHEMBL4851594
7.23	IC50	58.6	nM	CHEMBL4866637
7.20	IC50	63.8	nM	CHEMBL4862619
7.17	IC50	67	nM	CHEMBL4872300
7.16	Kd	70	nM	CHEMBL4848701
7.15	Kd	71	nM	CHEMBL4873093
7.15	Kd	71	nM	CHEMBL4780673
7.00	Kd	100	nM	CHEMBL3823478
6.94	IC50	113.8	nM	CHEMBL4852588
6.92	EC50	120	nM	CHEMBL4873042
6.92	Kd	120	nM	CHEMBL4461619
6.89	Ki	130	nM	CHEMBL4069412
6.84	IC50	145.4	nM	CHEMBL4853486
6.80	IC50	157.3	nM	CHEMBL4861221
6.77	IC50	170	nM	CHEMBL4848138
6.70	Kd	200	nM	CHEMBL4863631
6.70	Kd	200	nM	CHEMBL4461619
6.66	IC50	220	nM	CHEMBL4101756
6.64	EC50	228	nM	CHEMBL4461619
6.60	IC50	250	nM	CHEMBL4850516
6.54	IC50	290	nM	CHEMBL4866748
6.54	IC50	287.6	nM	CHEMBL4863921
6.51	IC50	310	nM	CHEMBL4870218
6.46	IC50	350	nM	CHEMBL4461619
6.43	IC50	370	nM	CHEMBL4848082
6.42	IC50	380	nM	CHEMBL4863631
6.37	Kd	428	nM	CHEMBL4846718
6.37	IC50	430	nM	CHEMBL4461619
6.26	IC50	550	nM	CHEMBL4877696
6.16	IC50	700	nM	CHEMBL4850913
6.16	IC50	698.3	nM	CHEMBL4861375
6.10	IC50	800	nM	CHEMBL4855881
6.10	IC50	790	nM	CHEMBL4863529
6.04	Kd	917	nM	CHEMBL4574669
6.02	IC50	950	nM	CHEMBL4065579
6.01	IC50	970	nM	CHEMBL4877118

PubChem BioAssay actives

66 with measured affinity, of 206 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-[4-(2-aminoethyl)anilino]-4-chloro-2-methylpyridazin-3-one	1769023: Binding affinity to BPTF (unknown origin) by by BROMOscan method	kd	0.0063	uM
5-[4-(2-aminoethyl)anilino]-4-bromo-2-methylpyridazin-3-one	1769023: Binding affinity to BPTF (unknown origin) by by BROMOscan method	kd	0.0093	uM
6-[1-[3-(dimethylamino)propyl]indol-5-yl]-2-methylsulfonyl-N-propylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.0160	uM
7-(1-cyclopropylpyrazol-4-yl)-2-[2-fluoro-4-(4-methylpiperazin-1-yl)sulfonylanilino]-3-methyl-1,9a-dihydropyrido[1,2-a]pyrimidin-4-one	1764122: Inhibition of BPTF in human HEK293 cells by NanoBRET assay	ic50	0.0160	uM
N,N-dimethyl-3-[5-(2-methylsulfonyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)indol-1-yl]propan-1-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.0269	uM
6-[1-[3-(dimethylamino)propyl]indol-5-yl]-N-ethyl-2-methylsulfonylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.0288	uM
6-[1-[3-(dimethylamino)propyl]indol-5-yl]-N-methyl-2-methylsulfonylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.0327	uM
6-[1-[2-(dimethylamino)ethyl]indol-5-yl]-N-methyl-2-methylsulfonylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.0369	uM
4-chloro-5-[4-[3-(dimethylamino)propyl]anilino]-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.0560	uM
6-[1-[3-(dimethylamino)propyl]-3-methylindol-5-yl]-2-methylsulfonyl-N-propylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.0586	uM
6-[1-[3-(dimethylamino)propyl]indol-5-yl]-N-methyl-2-methylsulfinylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.0593	uM
6-[1-[3-(dimethylamino)propyl]-7-methoxyindol-5-yl]-2-methylsulfonyl-N-propylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.0638	uM
7-(1-cyclopropylpyrazol-4-yl)-2-[2-fluoro-4-(4-methylpiperazin-1-yl)sulfonylanilino]-3-methylpyrido[1,2-a]pyrimidin-4-one	1770707: Binding affinity to BPTF (unknown origin)	kd	0.0710	uM
4-[4-[(dimethylamino)methyl]-3,5-dimethoxyphenyl]-2-methyl-2,7-naphthyridin-1-one	2191061: Binding affinity to FALZ (unknown origin) assessed as dissociation constant by bromoKdselect analysis	kd	0.1000	uM
N-butyl-6-[1-[3-(dimethylamino)propyl]indol-5-yl]-2-methylsulfonylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.1138	uM
6-[4-[3-(dimethylamino)propoxy]phenyl]-2-methylsulfonyl-N-(3-pyrazol-1-ylpropyl)pyrimidin-4-amine	1770707: Binding affinity to BPTF (unknown origin)	kd	0.1200	uM
6-[1-[3-(dimethylamino)propyl]indol-5-yl]-2-methylsulfinyl-N-propylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.1454	uM
N,N-dimethyl-3-[3-methyl-5-(2-methylsulfonyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)indol-1-yl]propan-1-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.1573	uM
4-chloro-5-[4-[2-(dimethylamino)ethyl]anilino]-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.1700	uM
2-[4-[4-(aminomethyl)anilino]-5-chloro-6-oxopyridazin-1-yl]acetonitrile	1769023: Binding affinity to BPTF (unknown origin) by by BROMOscan method	kd	0.2000	uM
5-[2-(aminomethyl)anilino]-4-chloro-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.2200	uM
4-chloro-2-methyl-5-(1,2,3,4-tetrahydroisoquinolin-6-ylamino)pyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.2500	uM
N-butan-2-yl-6-[1-[3-(dimethylamino)propyl]indol-5-yl]-2-methylsulfonylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.2876	uM
5-[4-(aminomethyl)anilino]-4-chloro-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.2900	uM
4-chloro-5-[4-[(dimethylamino)methyl]anilino]-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.3100	uM
4-chloro-2-methyl-5-(1,2,3,4-tetrahydroisoquinolin-7-ylamino)pyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.3700	uM
3-methyl-2-[[(3R,5R)-1-methyl-5-phenylpiperidin-3-yl]amino]-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-one	1764118: Binding affinity to BPTF (unknown origin) by isothermal titration calorimetry	kd	0.4280	uM
5-[4-(aminomethyl)anilino]-4-chloro-2-ethylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.5500	uM
6-(1H-indol-5-yl)-N-methyl-2-methylsulfonylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	0.6983	uM
4-chloro-5-(4-fluoroanilino)-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.7000	uM
5-[4-(aminomethyl)anilino]-4-chloro-2-propan-2-ylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.7900	uM
5-[3-(aminomethyl)anilino]-4-chloro-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.8000	uM
2-[[(3R,5R)-5-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-methylpiperidin-3-yl]amino]-3-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-one	1554037: Binding affinity to human N-terminal His-tagged FALZ by isothermal titration calorimetry	kd	0.9170	uM
5-anilino-4-chloro-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.9500	uM
N-[[4-[(5-chloro-1-methyl-6-oxopyridazin-4-yl)amino]phenyl]methyl]acetamide	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	0.9700	uM
4-bromo-2-methyl-5-[[(3R,5R)-1-methyl-5-phenylpiperidin-3-yl]amino]pyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	1.5000	uM
4-[(2-amino-3-chloro-4-hydroxy-5-methylphenyl)diazenyl]-N-pyridin-2-ylbenzenesulfonamide	1054708: Displacement of fluorescein-labeled MS239 from recombinant human BPTF after 1 hr by fluorescence anisotropy assay	ki	1.6200	uM
4-[(2-amino-4-hydroxy-3,5-dimethylphenyl)diazenyl]-N-pyridin-2-ylbenzenesulfonamide	1054708: Displacement of fluorescein-labeled MS239 from recombinant human BPTF after 1 hr by fluorescence anisotropy assay	ki	1.7000	uM
N-methyl-2-methylsulfonyl-6-quinolin-5-ylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	1.7000	uM
ethyl N-[5-[3-(methanesulfonamido)-4-methylphenyl]-3-methyl-3aH-pyrazolo[4,3-b]pyridin-7-yl]carbamate	1770706: Binding affinity to human BPTF by isothermal titration calorimetry	kd	1.8000	uM
6-[1-[3-(dimethylamino)propyl]indol-6-yl]-N-methyl-2-methylsulfonylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	2.1000	uM
methyl 3-[[1-[2-(4-fluoroanilino)pyrimidin-4-yl]pyrrolidin-3-yl]carbamoylamino]benzoate	1289210: Binding affinity to BPTF (unknown origin) by isothermal titration calorimetric analysis	kd	2.8000	uM
5-(4-aminoanilino)-4-chloro-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	3.2000	uM
4-chloro-2-methyl-5-(5,6,7,8-tetrahydronaphthalen-2-ylamino)pyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	3.9000	uM
4-chloro-2-methyl-5-[[(3R)-pyrrolidin-3-yl]amino]pyridazin-3-one	1770708: Binding affinity to BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells by SPR analysis	kd	6.0000	uM
4-[(2-amino-4-hydroxy-5-methylphenyl)diazenyl]-N-pyridin-2-ylbenzenesulfonamide	1054708: Displacement of fluorescein-labeled MS239 from recombinant human BPTF after 1 hr by fluorescence anisotropy assay	ki	6.0600	uM
5-(azepan-3-ylamino)-4-chloro-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	7.7000	uM
N-methyl-2-methylsulfonyl-6-phenylpyrimidin-4-amine	1770672: Inhibition of N-terminal GST-tagged human BPTF (2914 to 3037 residues) expressed in Escherichia coli BL21-CodonPlus (DE3) cells by HTRF assay	ic50	7.8000	uM
5-(azetidin-3-ylamino)-4-chloro-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	8.7000	uM
5-chloro-4-[2-(dimethylamino)ethylamino]-2-methylpyridazin-3-one	1769009: Inhibition of HIS9-tagged BPTF (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by AlphaScreen assay	ic50	10.0000	uM

CTD chemical–gene interactions

52 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression, affects expression, affects cotreatment	9
trichostatin A	affects cotreatment, decreases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Quercetin	increases expression, increases phosphorylation	2
Dronabinol	increases expression	2
Tretinoin	affects expression, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	increases methylation	1
2-butenal	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
LDN 193189	decreases expression, affects cotreatment	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1

ChEMBL screening assays

125 unique, capped per target: 123 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3089617	Binding	Displacement of fluorescein-labeled MS239 from recombinant human BPTF after 1 hr by fluorescence anisotropy assay	Structure-guided design of potent diazobenzene inhibitors for the BET bromodomains. — J Med Chem
CHEMBL5723061	Functional	Affinity Biochemical interaction: (AlphaScreen) EUB0000233b BPTF	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B5NA	PGPC1_73	Induced pluripotent stem cell	Female
CVCL_SF45	HAP1 BPTF (-) 1	Cancer cell line	Male
CVCL_SF46	HAP1 BPTF (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

299 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays